Human antibodies reactive to N eu G c GM 3 ganglioside have cytotoxic antitumor properties

• Published in: European journal of immunology 2013-03, Vol.43 (3), p.826-837
• Main Authors: Rodríguez‐Zhurbenko, Nely, Martínez, Darel, Blanco, Rancés, Rondón, Teresa, Griñán, Tania, Hernández, Ana María
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201242693

N ‐ glycolylated gangliosides are not naturally expressed in healthy human tissues but are overexpressed in several tumors. We demonstrate the existence of antibodies that bind ( N‐ glycolylneuraminyl)‐lactosylceramide ( N eu G c GM 3) and are detectable in the sera of 65 from the 100 donors (65%) tested by ELISA . From those 65 N eu G c GM 3 antibody‐positive donors, 35 had antibodies that were able to recognize and kill N eu G c GM 3‐expressing tumor cells by a complement‐mediated mechanism. After complement inactivation, 11 of the 35 positive sera showed a direct cytotoxic effect on the tumor cells. This complement‐independent cytotoxicity was dependent on the presence of antigen on the membrane and resembles an oncotic necrosis cell death. Both the levels of anti‐ N eu G c GM 3 antibodies in the sera as well as the percentage of healthy donors with this immunity decreased with the age of the donor. In contrast to age and gender‐matched healthy donors, we could only detect low reactivity against N eu G c GM 3 in the sera of six out of 53 non‐small cell lung cancer patients. These results suggest the existence of antibodies against N eu G c GM 3 with antitumor immune surveillance functions, reinforcing the importance of N ‐ glycolylated gangliosides as antitumor targets.